Medical glass element

ABSTRACT

A material that is less populated by biofilms than known materials and is well tolerated by the body is provided. The material is an element introducible into or attachable on a human or animal body and includes a glass and/or glass ceramic and/or ceramic material at least in some areas thereof, which inhibits the formation of biofilms and/or on which human or animal cells grow if the element is introduced into the human or animal body or attached thereto, wherein the glass and/or glass ceramic material comprises at least: SiO 2  in a range from 60 to 75 wt % and ZnO in a range from 1 to 7 wt %.

CROSS REFERENCE TO RELATED APPLICATION

This application claims benefit under 35 U.S.C. §119(a) of German PatentApplication No. DE 10 2015 115 958.9 filed Sep. 22, 2015, the entirecontents of which are incorporated herein by reference.

BACKGROUND

1. Field of the Invention

The invention relates to an element introducible into or attachable on ahuman or animal body, comprising a glass and/or glass ceramic and/orceramic material at least in some areas thereof. Furthermore, theinvention relates to a glass and/or glass ceramic and/or ceramicmaterial for such an element, and to the use of a corresponding glassand/or glass ceramic and/or ceramic material for producing an elementintroducible into or attachable on a human or animal body.

2. Description of Related Art

Biofilms are complex communities of microorganisms in nutrient-richaqueous systems. Their formation is related to the adhesion andcolonization of surfaces through the production of extracellular stickypolymers. The formation of biofilms is also referred to as micro foulingand constitutes the first step of macro fouling, which means thecolonization or development of macroscopic fouling organisms.

In the medical field, components that are permanently present in or onthe body, such as catheters, prostheses, artificial heart valves,implants, pacemakers, and the like are highly susceptible to microfouling. This is accompanied by the risk of biofilm-associated diseasesand infections.

Biofilms are largely insensitive to environmental factors such asultraviolet radiation and to chemical treatments with, e.g., detergents,i.e. surface active components. Moreover, biofilms hardly respond toantibiotics and exhibit protection against the immune system of thehost. It is estimated that S. aureus and S. epidermidis are causingabout 40% to 50% of the infections on artificial heart valves andbetween about 50% and 70% of the biofilm infections on catheters.

SUMMARY

An object of the invention is to provide a material that is lesspopulated by biofilms than known materials for elements attachable onthe human or animal body or introducible into the body.

Another object of the invention is to provide a material which moreoveris well tolerated by the body.

These objects are achieved in a manner very surprisingly for a personskilled in the art by an element introducible into or attachable on ahuman or animal body, which comprises a glass and/or glass ceramicand/or ceramic material at least in some areas thereof, which inhibitsthe formation of biofilms and/or on which human or animal cells grow ifthe element is introduced into the human or animal body or attachedthereto, wherein the glass and/or glass ceramic and/or ceramic materialcomprises at least: SiO₂ in a range from 60 to 75 wt %, and ZnO in arange from 1 to 7 wt %.

It is advantageous if the element inhibits the formation of biofilms.Alternatively it is possible and also advantageous if human or animalcells grow on the element when it is introduced in the human or animalbody or attached thereto. It is particularly advantageous if the elementboth inhibits the formation of biofilms and human or animal cells growon the element when it is introduced in the human or animal body orattached thereto. All these features are within the scope of theinvention.

The inventors have found that, surprisingly, the glass or glass ceramicor ceramic material inhibits the formation of biofilms on the one hand,and on the other, advantageously, human or animal cells grow on theglass or glass ceramic or ceramic material when the element isintroduced into the human or animal body or attached thereon. Accordingto the findings of the inventors, eukaryotic and prokaryotic cells showan opposite reaction to the glass or glass ceramic or ceramic materialwith the composition according to the invention. This is exploited bythe invention by using the glass and the glass ceramic and the ceramicfor components which come in contact with or in particular are evenintroduced into the human or animal body and for which high hygienerequirements are existing. The same material according to the inventionallows inhibition of an accumulation of biofilms on the one hand andpreferably also promotes compatibility and even ingrowth in or growth ofbody cells thereon. It has been found that eukaryotic cells are notaffected in terms of their growth and normal cell division (i.e. nospecial cell adhesion for eukaryotic cells). Thus, the materials of theinvention are not cytotoxic.

In the context of the present application the indication “wt %” is basedon the total amount of oxides, that is to say the given amounts of theconstituents of the glass and/or glass ceramic and/or ceramic materialsare specified in “wt % on oxide basis”.

“Element” refers to a body that may consist of solid material, but mayas well be formed with at least one cavity. The shaping of the inventiveelement is freely selectable by the skilled person within themanufacturing options for elements made of glass and/or glass ceramicand/or ceramic material, depending on the application of the element.Moreover, within the scope of the invention, the element may as well beprovided in the form of bulk material, for example as a powder, or as anadditive for suspensions.

The further constituent components or oxides of the glass or glassceramic or ceramic material will be selected for the relevantapplication by a person skilled in the art based on his expertise andalso in view of the later application, connection with other materials(e.g. metals or ceramics), the type of melting and/or furtherprocessing. Moreover, refining agents may be added.

“Growth of human or animal cells thereon” means that the glass and/orglass ceramic and/or ceramic material is not cytotoxic to these cellsand is compatible with blood (hemocompatible). The interaction betweenthe surface of the glass and/or glass ceramic and/or ceramic materialwith erythrocytes as the main components of blood and one of the firstcontact partners after systemic administration were determined byhemolysis and erythrocyte aggregation.

Cytotoxicity was determined by the inventors with respect to musclecells, Caco2 cells, and L929 mouse fibroblasts. To this end, the glassand/or glass ceramic material with the respective cells was cultured inDMEM (Life Technologies) for 48 hours. The experiments were performed at37° C. under an atmosphere of +5% CO₂. This corresponds to standardizedtests for cytotoxicity to eukaryotic cells. Cytotoxicity was evaluatedon the basis of cell growth and cell morphology. Morphological changesand cell damage were determined qualitatively from digital photographsby a light phase contrast microscope.

For determining hemolysis and erythrocyte aggregation, human red bloodcells were incubated on the relevant glass and/or glass ceramic materialfor two hours at 37° C. The red blood cells were obtained from bloodwhich was collected in heparinized tubes. The suspensions of red bloodcells were then used within 24 hours.

The release of hemoglobin was used to quantify a damaging effect of theglass and/or glass ceramic material on the erythrocyte membrane. Thetreatment of the red blood cells with PBS buffer and with a solution of1% Triton X-100 resulted in 0% and 100% hemolysis, respectively. Fordetermining hemolysis, hemoglobin release was determined byspectroscopic analysis of the supernatant at 544 nm. A release from 0 to2% of the total release was classified non-hemolytic, a release in therange between 2% and 5% of the total release was classified slightlyhemolytic, and a release of more than 5% of the total release wasclassified as hemolytic, according to the ASTM F756-08 standard.

For determining erythrocyte aggregation, micrographs were evaluated byclassification into three levels. In level 1, the red blood cellsremained discretely distributed in the suspension, without detectableaggregation. In level 2, moderate aggregation can be seen, with rouleauformation, but the majority of erythrocytes is discrete. This was foundin microscopic observations of known methodology (see Bauer et al.,Macromol. Biosci. 2012, 12, 986-998). In level 3, nearly all red bloodcells are aggregated to form clusters. For determining level 1, theerythrocytes were treated with PBS as a negative control. Positivecontrols were treated with 30 mg/mL 25 kDa branched polyethyleneimineand classified as level 3.

The term “inhibiting the formation of biofilms” means that compared toglasses and/or glass ceramics that are usually employed as a substratefor microbial colonization, such as borosilicate glass, e.g. applicant's“Borofloat 33”, or soda-lime glass (Paul Marienfeld GmbH), a smallersurface area is covered by biofilm if the glass of the invention and/orthe glass ceramic of the invention is used.

The coverage by biofilm can be determined by visualization, for example.The inventors performed appropriate experiments using a LSM510 confocallaser scanning microscope by scanning a surface area of 100 μm by 100 μm(microns) on the green channel (480/500 nm) and the red channel (490/635nm). A 40×10 water immersion objective was used for this purpose. Theimages of the biofilms were visualized using ZEN 9.0 software (CarlZeiss Microscopy GmbH).

The area covered by biofilm within an image is calculated based on aseparation of pixels from the background according to the brightnessthereof. A 16 bit image is divided into 256 gray levels (0=black;255=white). By applying a threshold according to Otsu, all covered areascan be reliably identified. The area covered by biofilm was calculatedwith respect to the total number of pixels of an image using ImageJ1.43u software.

A glass ceramic material usually is understood to be a material which ismade from the same starting materials as a glass, but for which duringprocessing the glass is transferred into a partially crystalline andpartially amorphous, i.e. glassy state before, during, or after molding,for example by selective temperature control. Even completedevitrification is possible and within the scope of the invention.

“Glass ceramic material” usually refers to a material in which bothcrystalline phases and amorphous phase, i.e. glass phases, coexist.Zones with crystalline phases may in particular be interconnected byglass phases. A glass ceramic can be considered a partially crystallizedglass so to speak, in which the degree of crystallization may widelyvary, even approaching 100%.

Also encompassed by the invention is the case where the material is aceramic, i.e. it is fully crystallized. Crystallization may inparticular be achieved by process control during the manufacturing ofthe material and/or further processing thereof, in particular by coolingand/or heating.

The crystalline phases may usually be embedded in the glass phase.

In an advantageous embodiment of the invention, the glass and/or glassceramic and/or ceramic material comprises at least the followingcomponents:

-   -   SiO₂ in a range from 60 to 75 wt %    -   R₂O in a range from 5 to 20 wt %    -   RO in a range from 0 to 10 wt %    -   Al₂O₃ in a range from 1 to 6 wt %    -   B₂O₃ in a range from 0 to 10 wt %    -   TiO₂ in a range from 0 to 8 wt %    -   ZnO 1 to 7 wt %    -   FeO 0 to 5 wt %, wherein R₂O is an oxide or a combination of        oxides selected from the group comprising Li₂O, Na₂O, and K₂O,        and wherein RO is an oxide or a combination of oxides selected        from the group comprising MgO and/or CaO and/or BaO and/or SrO.        The total amount of R₂O and/or RO may comprise one or more        oxides of the relevant specified group in any combination of the        oxides.

Iron oxide is added to the glass for achieving fusion using IR lamps orlasers performing at a wavelength of 1060 nm. Absorption shouldpreferably be between 2 and 20%. This is the case with FeO contents from2.7 to 5%. The thinner the wall thickness of the glass to be fused, thestronger should be the absorption and accordingly the higher should bethe FeO content. If during melting of the glass the iron is added in theform of Fe₂O₃, it must be ensured by appropriate melting control that asufficient amount of Fe(III) is reduced to Fe(II) in order to obtain thespecified FeO contents in the glass. Iron oxide may be present in theglass in different oxidation states and is specified in the form of FeOherein. A person skilled in the art will know how to convert this intoproportions of Fe(III) and Fe₂O₃, if he wishes to specify the proportionof Fe₂O₃, for instance for synthesis purposes.

In particular it has been found advantageous for the glass and/or glassceramic and/or ceramic material to comprise:

-   -   SiO₂ in a range from 60 to 70 wt %    -   R₂O in a range from 5 to 20 wt %    -   RO in a range from 0 to 10 wt %    -   Al₂O₃ in a range from 1 to 5 wt %    -   B₂O₃ in a range from 0 to 10 wt %    -   TiO₂ in a range from 0 to 8 wt %    -   ZnO in a range from 1 to 7 wt %    -   FeO in a range from 0 to 5 wt %, with    -   Na₂O in a range from 2 to 10 wt %, and/or    -   K₂O in a range from 3.5 to 10 wt %,    -   wherein R₂O is an oxide or a combination of oxides selected from        the group comprising Li₂O, Na₂O, and K₂O, and wherein RO is an        oxide or a combination of oxides selected from the group        comprising MgO and/or CaO and/or BaO and/or SrO.

It is of particular advantage if the glass and/or glass ceramic and/orceramic material is free of CuO, except for impurities. Impurities mayusually be present in a content of up to 0.3%. This means that the CuOcontent is advantageously from 0 to 0.3%, most advantageously 0%.

The described glass and/or glass ceramic and/or ceramic material ismoreover particularly suitable for producing hermetic feedthroughs,especially with titanium and/or several titanium alloys. In such afeedthrough, a functional element is usually held in a feedthroughopening of a carrier member by an insulating element therebyhermetically sealing the feedthrough opening. The carrier member may inparticular be a casing and/or a casing part, here in particular of acasing or casing component made of titanium or titanium alloys, and thefunctional element may in particular be an electrical conductor. Otherfunctional elements, such as e.g. optical fibers, waveguides, hollowwaveguides, tubes, capillaries, and the like are of course alsoencompassed by the invention. The insulating element is made of thedescribed glass and/or glass ceramic and/or ceramic material and forexample has the shape of a plug.

The suitability of the glass and/or glass ceramic and/or ceramicmaterial in particular for producing feedthroughs with titanium and/ortitanium alloys is due to the chemical compatibility with these metalsand/or the thermal expansion coefficients thereof. Particularlyadvantageously the coefficient of thermal expansion of the glass and/orglass ceramic and/or ceramic material is lower than that of titaniumand/or the titanium alloy in question, so that a so-called compressionfeedthrough may be produced.

In such a case, when fusing the functional element to the carrier memberusing the insulating material, the carrier member will shrink onto theinsulating element so that at least at room temperature the carriermember will exert a compressive stress to the insulating element. Inthis manner the extraction force which is the force that is needed tourge the insulating element out of the carrier member can in particularbe significantly increased, and/or a reliable and permanentlyhermetically sealed feedthrough can be provided.

Particularly good results have been obtained with a glass and/or glassceramic and/or ceramic material comprising:

-   -   SiO₂ in a range from 62 to 66 wt %    -   Al₂O₃ in a range from 3.8 to 4.5 wt %    -   B₂O₃ in a range from 0 to 10 wt %    -   TiO₂ in a range from 3.5 to 4.5 wt %    -   ZnO in a range from 5 to 7 wt %    -   FeO in a range from 0.001 to 0.005 wt %    -   Na₂O in a range from 5.9 to 6.5 wt %, and    -   K₂O in a range from 8.3 to 9.1 wt %, where    -   SeO₂ may be present in a content of up to 0.04 wt %.

In particular, the glass and/or glass ceramic material may comprise acontent of Ag of less than 0.3 wt % and/or a content of P₂O₅ of lessthan 0.5 wt % and/or a content of F of less than 1 wt %. Particularlyadvantageously the proportion of Ag and/or P₂O₅ is selected so as to beas low as possible, especially if the glass and/or glass ceramicmaterial is free of these substances, except for impurities at the most.In particular, this includes the content of 0%. This lower limit alsoapplies to F₂. However, it may as well be advantageous if the glassand/or glass ceramic material includes a certain small percentage of F₂.Therefore, according to one advantageous embodiment a content of F₂ ofmore than 0 wt % up to less than 1 wt % is contemplated.

According to one advantageous embodiment of the invention it iscontemplated that for applications in or on the body the elementcomprises at least one casing or constitutes a casing which is designedfor accommodating active and/or passive electronic components, and inthis case the casing consists of the glass and/or glass ceramic materialat least in sections thereof, and/or the casing has at least one coatingmade of the glass and/or glass ceramic material at least in areasthereof. It is likewise possible that additionally or alternatively thecasing is provided with means for delivering active substances, such asa membrane and/or a valve, and the like. In this way, active substances,especially medicines, can be delivered in the body and advantageously ata predefined point, for example directly into the bloodstream.

In one embodiment, the element of the invention thus comprises orconstitutes a casing for electronic components which is made of theglass at least in sections thereof or on which the glass is applied as alayer at least in areas thereof.

In a particularly simple implementation, the casing comprises a tubemade of the glass and/or glass ceramic material. More particularly, theelement is a glass tube that is in particular sealed on one or both endsthereof. The element may furthermore be in the form of a casing forelectronic devices such as transponders or entire defibrillators,pacemakers, or labs-on-chip, or may be formed as a contact lens, forexample.

Furthermore within the scope of the invention, the element may be animplant, a hermetically sealed feedthrough, a vascular support, inparticular a stent, or a catheter or a similar component that can beintroduced into the human or animal body.

The invention also provides a glass and/or glass ceramic and/or ceramicmaterial for use as an element inhibiting the formation of biofilmsand/or as an antibacterial element, and/or as a region of an elementinhibiting the formation of biofilms and/or as an antibacterial regionof an element, and/or as a coating on or in an element inhibiting theformation of biofilms and/or an antibacterial coating on or in anelement which is introducible into or attachable on a human or animalbody; wherein the glass and/or glass ceramic and/or ceramic materialcomprises: SiO₂ in a range from 60 to 75 wt %, and ZnO in a range from 1to 7 wt %. In particular the element may be an element as describedabove.

Moreover, the invention relates to the use of a glass and/or glassceramic and/or ceramic material for producing an element that isintroducible into a human or animal body, in particular an elementimplantable into a human or animal body, or for producing an elementattachable on a human or animal body. In a preferred embodiment, theinvention relates to a glass and/or glass ceramic material as describedabove for producing implants, hermetic feedthroughs, vascular supports,in particular stents, catheters, artificial heart valves, casings forelectronic devices such as transponders or entire defibrillators,pacemakers, and labs-on-chip, as well as contact lenses and/or coatingson contact lenses, wherein in the case of use as a contact lens and/orcoating on contact lenses the content of coloring substances, e.g. ironoxide and other impurities should be selected as low as possible.

The use of the glass and/or glass ceramic and/or ceramic materialaccording to the invention as a transponder material has proved to beparticularly advantageous over known materials for this application.Transponder material is for instance employed for hermetic encapsulationof RFID transponders which are used for identification and tracking ofdomestic and farm animals, for example. The encapsulation with thedescribed material allows for protection of the electronic componentwithin the body, at the same time it protects the surrounding tissuefrom the electronics located in the interior of the encapsulation. Italso provides protection from environmental influences such as moistureand dirt when the transponder is worn on the body. In this case, theinhibitory activity against biofilm formation of the material accordingto the invention proves also advantageous. This also applies to medicalaids worn on the body such as contact lenses.

However, the transponders may as well be implanted, and in such anapplication the particularly good compatibility of the materialaccording to the invention with human or animal cells is particularlyfavorable. This also applies to the use of the glass and/or glassceramic and/or ceramic material of the invention as a casing or casingcomponent for another electronic medical device, such as an activeimplant, as well as for applications as a material for medical aids thatare introduced into the body, such as implants, vascular supports, inparticular stents, and catheters, artificial heart valves, meteringdevices for active substances, and the like, and combinations of suchitems.

The element of the invention is suitable in conjunction with all medicaldevices or aids such as needles, suture materials, and staples, and thelike, which are used on or in the body.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be explained in more detail by way of exemplaryembodiments and with reference to the accompanying drawings. Identicaland similar components are designated with the same reference numerals,and features of the various exemplary embodiments can be combined and/orsubstituted by each other.

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

FIG. 1 shows an analysis and visualization of biofilm growth afterculturing for 24 hours: initial data analysis of biofilm-coveredsurface, cumulatively for all bacteria;

FIG. 2 shows an analysis and visualization of biofilm growth afterculturing for 24 hours: quantitative analysis of biofilm-covered surfacefor each of the bacterial species;

FIG. 3 shows an analysis and visualization of biofilm growth afterculturing for 24 hours: representative images of biofilms on soda-limeglass;

FIG. 4 shows an analysis and visualization of biofilm growth afterculturing for 24 hours: representative images of biofilms on glassaccording to a first embodiment of the invention;

FIG. 5 shows cytotoxicity and hemocompatibility of soda-lime glass andseveral borosilicate glasses: representative images of cultured musclecells, Caco2 cells, and L929 mouse cells;

FIG. 6 shows cytotoxicity and hemocompatibility of soda-lime glass andseveral borosilicate glasses: data relating to hemolysis;

FIG. 7 shows cytotoxicity and hemocompatibility of soda-lime glass andseveral borosilicate glasses: data relating to erythrocyte aggregation;

FIG. 8 shows cytotoxicity and hemocompatibility of soda-lime glass andseveral borosilicate glasses: representative images of cultured cells ofMSSA, Enterococcus faecalis, Enterococcus faecium, Escherichia coli,Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus mirabilis,Staphylococcus epidermis;

FIGS. 9a, 9b, and 9c schematically illustrate an implantable casing foran electronic component according to a first embodiment of theinvention; and

FIG. 10 schematically illustrates a vascular support according toanother embodiment of the invention.

DETAILED DESCRIPTION

In order to investigate the inhibition of biofilm growth and the growthof human and animal cells, experiments were performed with differentglasses. Glasses “BF1” and “BF₂” were used as embodiments of theinvention. Glasses “VG1”, “VG2”, and “VG3” were examined as comparativeexamples.

Table 1 below gives an overview of the chemical composition of theinvestigated glasses and glass ceramics:

Content (wt %) VG1 VG2 VG3 BF1 BF2 SiO₂ 72.48 81.19 61.59 63.03 63.06Al₂O₃ 1.21 2.41 16.96 4.11 4.11 Na₂O 14.36 3.52 12.32 6.08 6.08 K₂O 1.210.08 4.14 8.51 8.51 MgO 4.32 0.00 3.94 0.00 0.00 CaO 6.43 0.00 0.00 0.000.00 ZnO 0.00 0.00 0.00 5.83 5.83 B₂O₃ 0.00 12.76 0.00 8.22 8.22 CeO₂0.00 0.00 0.30 0.00 0.00 TiO₂ 0.00 0.00 0.00 3.98 4.11 SnO₂ 0.00 0.000.40 0.00 0.00 Sb₂O₃ 0.00 0.00 0.00 0.20 0.00 F₂ 0.00 0.00 0.30 0.000.000 FeO 0.01 0.04 0.05 0.05 0.05 SeO₂ 0.00 0.00 0.00 0.00 0.03 Total100.00 100.00 100.00 100.00 100.00

The glasses were tested in the form of sheets. Initially, the sheetswere ultrasonically cleaned in 1% Deconex® 12 PA (Borer advancedcleaning solutions) at 40° C. for 15 min. The reagent was first removedwith warm tap water and then by washing with deionized water.Thereafter, the sheets were treated using ultrasound in deionized waterat 40° C. for 5 min. Finally, the sheets were dried in a nitrogenstream.

For the tests of biofilm formation, eight typical representatives ofnosocomial infections were examined, namely MSSA: Staphylococcus aureus,methicillin-sensitive (ATCC 29213), Staphylococcus epidermis (Pp 62a),Enterococcus faecalis (ATCC 29212), Enterococcus faecium (SMZ 20477),Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603),Pseudomonas aeruginosa (PA01), and Proteus Mirabilis (VBK 4479).

The bacterial seed stocks were stored at −80° C. in 10 vol % glycerolsolution. Prior to culturing in liquid medium, a strand of frozenbacteria was plated on lysogeny broth (LB) agar (1.5%) sheets andincubated overnight at 37° C. A single colony of each of the strainspathogenic for humans was cultured overnight in Mueller-Hinton (MH)medium at 37° C.

For biofilm formation, the cultures were freshly seeded in MH medium ata dilution of 1:1000 and were filled into 8×2 sections of siliconestructures (SCHOTT Nexterion) attached to the glass sheets. Biofilmswere grown at 37° C. over a period of 24 hours without shaking.

The biofilms were stained using the LIVE/DEAD BacLight BacterialViability Kit (Life Technologies). After staining, the bacterialsupernatant was carefully removed, and the biofilms were carefullywashed once with 300 μL (microliters) of a 0.9% NaCl solution. Then,they were embedded in Fluoromount-G (SouthernBiotech, BIOZOL) andcovered with Nexterion® glass cover sheets (SCHOTT Nexterion).Visualization of the biofilms was performed as described above.

FIGS. 1 to 4 show results of the analysis and visualization of biofilmgrowth after culturing for 24 hours. The symbol p represents the p-valueor significance value which is an indicator for the evaluation ofstatistical tests. In biological sciences, a threshold of 5% has beenestablished (maximum error probability or significance level α=0.05).That means: If the probability for a result to be coincidental is lessthan 5%, it is considered to be “significant” (p<0.05).

The statistical analysis of the biofilm-covered surface areas(cumulative for all species) is given in Table 2 below, wherein N is thenumber of experiments, and SEM is “standard error of mean.”

Biofilm surface area Biofilm Degree of biofilm (%) thickness homogeneityGlass type Mean SEM (mm) (% incomplete) VG1 (N = 24) 69.33 7.041 10 to30 <10 VG2 (N = 27) 21.03 1.500 10 to 30 <20 VG3 (N = 25) 14.32 1.875 10to 30 <50 BF1 (N = 27) 0.76 0.294  4 to 10 >95 BF2 (N = 25) 0.07 0.026 4 to 10 >95

All investigated human-pathogenic strains grew well on the surfaces ofthe glass corresponding to VG1 and on the sheets with the composition ofVG2 and VG3. After 24 hours, most of the bacteria lived, which can beverified by green staining using SYTO9. The sporadic dead cells (stainedred by propidium iodide) correspond to the usual decrease in biofilms.

On glasses BF1 and BF₂ according to the invention, all investigatedhuman-pathogenic germs showed reduced biofilm formation. Biofilmthickness is greatly reduced and is in a range between 4 μm and 10 μm(microns). In addition, the biofilms on the glasses of the inventionexhibit morphological modifications with diffuse and porous structures.The surface areas actually covered by biofilms, namely 0.76±0.294% and0.07±0.026% are greatly reduced in comparison to the other investigatedglasses. Furthermore, the existing biofilms on the glasses of theinvention exhibit greatly increased porosity of more than 95% incomparison to the other investigated glasses. Like the well grownbiofilms on VG1, VG2, and VG3, the diminished biofilms only show a smallnumber of dead cells.

These results surprisingly indicate that the chemical composition of theinventive materials BF1 and BF₂ prevents the first step for adhesion ofbacteria. So far, the investigated glasses according to the inventionwere used as resistant covers for touch panels of navigation devicesintegrated in automobiles, or as substrates for capacitive sensors andfilters for camera modules in mobile phones, and as casing for CCD imagesensors. Therefore, a person skilled in the field of microbiology nevercame into contact with these glasses.

FIGS. 5 to 8 illustrate results of in vitro determined cytotoxicity andhemocompatibility of soda-lime glass and different borosilicate glasses.

In order to evaluate modifications in cell morphology and growthperformance, muscle cells, Caco2 cells, and L929 mouse fibroblasts werecultured on the different glasses for 48 hours. Compared with controlcells in cell culture flasks, no changes in cell morphology and growthperformance were found for all glasses. As can be seen from the imagesof FIG. 5, no apoptotic cells and abnormalities can be found in the cellenvironment. None of the examined glass compositions showed any signs ofcytotoxicity.

For investigating hemolysis, erythrocytes were incubated on the glasssurfaces for two hours. As proved by the results plotted in FIG. 6, noneof the glasses exhibits proportions of hemolysis of more than 0.57%,regardless of the glass composition. According to the ASTM F756-00standard, a hemoglobin release between 0 and 2% is considerednon-hemolytic. This indicates that there is no detectable disorder ofthe membranes of the red blood cells.

Additionally it was investigated to what extent the types of materialare capable of causing aggregation of erythrocytes. Aggregation oferythrocytes is an undesirable phenomenon which leads to side effects onthe circulation and even lethal toxicity. The aggregation oferythrocytes was visualized microscopically after two hours ofincubation on the glass surfaces. Treatment with 25 kDa bPEI at 30 mg/mLas a positive control resulted in the formation of aggregates (level 3according to the classification discussed above). However, as shown inFIG. 7, no aggregation of red blood cells was found for any of theinvestigated materials. Moreover, all glass compositions exhibited verygood hemocompatibility.

Among the germs used, S. epidermis basically showed low tendency to formbiofilms on the glasses. By contrast, K. pneumoniae and MSSA showed anelevated tendency to adhesion and growth on the glass surfaces, as isillustrated by the images of FIG. 8. However, even for these germsbiofilm formation is significantly reduced on the glasses of theinvention.

Thus, glasses and/or glass ceramics and/or ceramics with the compositionaccording to the invention are particularly suitable for the developmentof highly efficient anti-biofilm surfaces or coatings. Compared to thecomparative examples VG1 to VG3, the glass and/or glass ceramic and/orceramic material of the invention exhibits reduced biofilm adherence,increased biofilm porosity, and reduced biofilm thickness, andfurthermore is excellently cytocompatible and hemocompatible withouttoxicity to eukaryotic cells.

With these surprising properties, diverse applications of the inventionare possible in the field of medicine.

FIGS. 9a-9c and 10 illustrate exemplary applications for the glass orglass ceramic material of the invention.

FIGS. 9a-9c illustrates a casing 1 for electronic components 2.Transponder casings, also known as transponders tubes, are easilymanufactured as sections of tubing. One end is then sealed by fusesealing, for example. Such a casing for a transponder is illustrated inFIG. 9A. An electronic component known as transponder is then introducedinto the tube through the still open end shown on the right side in thefigure, see FIG. 9B. The transponder may e.g. comprise an RFID chip or asensor. The still open end of the tube may then be closed by heatapplication, for example using a laser and/or infrared radiation, sothat the casing will then advantageously be hermetically sealed, asshown in FIG. 9C. In a preferred embodiment of the invention the casingis autoclavable.

The proportion of FeO in the glass and/or glass ceramic and/or ceramicmaterial may promote the sealing of the tube in particular when a laserand/or infrared radiation is employed, in particular because itincreases absorption of the material in the infrared spectral range.

Typical dimensions for such transponder casings are in a range of up to10 mm, preferably in a range of up to 5 mm, more preferably in a rangebetween 1 mm and 4 mm for the outer diameter, and in a range of up to100 mm, preferably in a range of up to 70 mm, more preferably in a rangebetween 5 mm and 50 mm in length. The wall thickness is in particular ina range of up to 2 mm, preferably in a range of up to 1.5 mm, morepreferably in a range between 0.03 mm and 1.1 mm.

It is likewise possible for the element in the form of a tube section,for example, to be equipped with means permeable for an activesubstance, such as a membrane, on at least one end thereof, and to havean active substance deposited in the interior thereof. In this way, animplant for administering active substances can easily be produced.

It is also possible to integrate electronic components in such animplant for administering active substances, and the electroniccomponent may in particular control the conditions of and/or triggeractive substance release, in particular the timing and/or amount ofactive substance release. This electronic component may in particular aswell be designed so as to be capable of communicating, via electricalconductors, e.g. wires and/or contacts, but also by wirelesscommunication, with electronic devices outside the body which may inparticular transmit control and/or sensor signals to the electroniccomponent within the implant. In this way the described implant may bepart of a more complex diagnostic and/or treatment apparatus.

It is similarly possible for substances, in particular liquids from thehuman or animal body to enter into the interior of the implant throughthe permeable means in order to be then analyzed there by the one ormore electronic components. Data obtained from the analysis may betransmitted to electronic devices outside the human or animal body.

FIG. 10 illustrates a stent 3 as a further possible application of theglass or glass ceramic material according to the invention. Stent 3 isinserted in a hollow organ 4, for example a blood vessel. Stent 3 ismade of a metal mesh, for example of titanium. The enlarged detail A onthe right side of the figure shows a portion of a metal filament 5 ofthe metal mesh. According to the invention, metal filaments 5 have acoating 6, at least in areas thereof, which is made of the glass and/orglass ceramic material in accordance with a composition as describedabove. In this manner, susceptibility of the stent 3 for microbialcolonization is significantly reduced as compared to known materials.Moreover, a stent coated in this manner is very well tolerated by thehuman or animal body.

It will be apparent to those skilled in the art that the invention isnot limited to the examples described above, but rather may be varied inmany ways. In particular it is possible for the features of theindividual illustrated examples to be combined or substituted for eachother.

What is claimed is:
 1. An element introducible into or attachable on ahuman or animal body, comprising a material selected from the groupconsisting of glass, glass ceramic, ceramic, and any combinationsthereof, wherein the material inhibits the formation of biofilms,wherein the material comprises at least: SiO₂ in a range from 60 to 75wt % and ZnO in a range from 1 to 7 wt %.
 2. The element as claimed inclaim 1, wherein the material comprises: SiO₂ in a range from 60 to 75wt %, R₂O in a range from 5 to 20 wt %, RO in a range from 0 to 10 wt %,Al₂O₃ in a range from 1 to 6 wt %, B₂O₃ in a range from 0 to 10 wt %,TiO₂ in a range from 0 to 8 wt %, ZnO in a range from 1 to 7 wt %, andFeO 0 to 5 wt %, wherein R₂O is an oxide or a combination of oxidesselected from the group consisting of Li₂O, Na₂O, and K₂O, and whereinRO is an oxide or a combination of oxides selected from the groupconsisting of MgO, CaO, BaO, SrO, and any combinations thereof.
 3. Theelement as claimed in claim 1, wherein the material comprises: SiO₂ in arange from 60 to 70 wt %, R₂O in a range from 5 to 20 wt %, RO in arange from 0 to 10 wt %, Al₂O₃ in a range from 1 to 5 wt %, B₂O₃ in arange from 0 to 10 wt %, TiO₂ in a range from 0 to 8 wt %, ZnO in arange from 1 to 7 wt %, FeO in a range from 0 to 5 wt %, and Na₂O in arange from 2 to 10 wt % and/or K₂O in a range from 3.5 to 10 wt %;wherein R₂O is an oxide or a combination of oxides selected from thegroup consisting of Li₂O, Na₂O, and K₂O, and wherein RO is an oxide or acombination of oxides selected from the group consisting of MgO, CaO,BaO, SrO, and any combinations thereof.
 4. The element as claimed inclaim 1, wherein the material comprises: a content of Ag of less than0.3 wt %; and/or a content of P₂O₅ of less than 0.5 wt %; and/or acontent of F of less than 1 wt %.
 5. The element as claimed in claim 1,further comprising an electronic component casing, wherein the materialforms at least a portion of the electronic component casing.
 6. Theelement as claimed in claim 1, further comprising an electroniccomponent casing, wherein the material is a coating on at least aportion of the electronic component casing.
 7. The element as claimed inclaim 1, wherein the material is formed into a tube.
 8. The element asclaimed in claim 1, wherein the material configured for use as aninsulating component of a feedthrough of a casing made of stainlesssteel or titanium and/or a titanium alloy.
 9. The element as claimed inclaim 1, wherein the element is configured for a use selected from thegroup consisting of an implant, a vascular support, a stent, a catheter,a transponder casing, a defibrillator, a pacemaker, a lab-on-chip, acontact lenses, and a contact lens coating.
 10. A material capable ofinhibiting the formation of biofilms when introducible into or on ahuman or animal body, comprising a glass and/or glass ceramic and/orceramic that comprises SiO₂ in a range from 60 to 75 wt % and ZnO in arange from 1 to 7 wt %.
 11. The material as claimed in claim 10, whereinthe glass and/or glass ceramic and/or ceramic material comprises: SiO₂in a range from 60 to 75 wt %, R₂O in a range from 5 to 20 wt %, RO in arange from 0 to 10 wt %, Al₂O₃ in a range from 1 to 6 wt %, B₂O₃ in arange from 0 to 10 wt %, TiO₂ in a range from 0 to 8 wt %, ZnO 1 to 7 wt%, and FeO 0 to 5 wt %, wherein R₂O is an oxide or a combination ofoxides selected from the group consisting of Li₂O, Na₂O, and K₂O, andwherein RO is an oxide or a combination of oxides selected from thegroup consisting of MgO, CaO, BaO, SrO, and any combinations thereof.12. The material as claimed in claim 10, wherein the glass and/or glassceramic and/or ceramic material comprises: SiO₂ in a range from 60 to 70wt %, R₂O in a range from 5 to 20 wt %, RO in a range from 0 to 10 wt %,Al₂O₃ in a range from 1 to 5 wt %, B₂O₃ in a range from 0 to 10 wt %,TiO₂ in a range from 0 to 8 wt %, ZnO in a range from 1 to 7 wt %, FeOin a range from 0 to 5 wt %, and Na₂O in a range from 2 to 10 wt %,and/or K₂O in a range from 3.5 to 10 wt %.
 13. The material as claimedin claim 10, wherein the glass and/or glass ceramic and/or ceramicmaterial comprises: a content of Ag of less than 0.3 wt %; and/or acontent of P₂O₅ of less than 0.5 wt %; and/or a content of F of lessthan 1 wt %.
 14. The material as claimed in claim 10, wherein the glassand/or glass ceramic and/or ceramic material is configured as an elementintroducible into a human or animal body.
 15. The material as claimed inclaim 10, wherein the glass and/or glass ceramic and/or ceramic materialis configured as an element implantable into a human or animal body. 16.The material as claimed in claim 10, wherein the glass and/or glassceramic and/or ceramic material is configured as an element attachableon a human or animal body.
 17. The material as claimed in claim 10,wherein the glass and/or glass ceramic and/or ceramic material isconfigured as an element selected from the group consisting of animplant, a casing feedthroughs of an implants, a vascular support, astent, a catheter, an artificial heart valve, a casing of a transponder,a casing of a defibrillator, a casing of a pacemaker, a lab-on-chip, acontact lens, and a coating for a contact lens.